The incidence of type 2 diabetes mellitus (DM) continues to rise rapidly in the United States. During heat stress, individuals with type 2 DM appear to be at increased risk for development of heat illness. In humans, cutaneous vasodilator responsiveness to thermal stress is essential for the heat dissipation necessary to maintain internal body temperature during heat exposure or exercise. Cutaneous vascular complications of type 2 DM are well-recognized, and local vasodilator responsiveness appears to be impaired in this disease, although the mechanisms for these changes are not clear. Impaired thermoregulatory vasodilation in the skin of patients with type 2 DM could contribute to the increased risk of heat illness; however, no information exists regarding cutaneous vasodilation during whole body heat stress in patients with type 2 DM. In this application, we propose to use laser-Doppler measurements of skin blood flow, measurements of forearm blood flow by venous occlusion plethysmography, and local pharmacological blockade in combination with (a) direct (local) heating of the skin, and (b) whole-body heating in patients with type 2 DM and age-matched controls to address the following specific aims: (1) To test whether local thermal control of cutaneous vasodilation is diminished with type 2 DM. (2) To quantify changes in contributions of sensory nerve and nitric oxide mechanisms to local warming vasodilation in type 2 DM. (3) To test whether the reflex cutaneous vasodilator response to whole body heat stress is diminished with type 2 DM. (4) To test whether any changes in reflex vasodilation during whole body heat stress are due to decreased sympathetic active vasodilation in the skin, and whether a decreased contribution of nitric oxide is involved. Our assessment of four mechanisms of skin blood flow regulation in patients with type 2 DM compared to control subjects matched for age and body size will provide important insight into potentially dangerous impairments of thermoregulatory control of skin blood flow in these patients.